Biological Properties of Heparins Modified with an Arylazopyrazole-Based Photoswitch.

Unfractionated heparin (UFH) and enoxaparin (Enox) were substituted with a photoswitch (PS) showing quantitative trans-cis and cis-trans photoisomerizations. Long half-life of the cis photoisomer enabled comparison of the properties of heparins substituted with both PS photoisomers. Hydrodynamic diameter, D _h , of UFH-PS decreased upon trans-cis photoisomerization, the change being more pronounced for UFH-PS with a higher degree of substitution (DS), while D _h of Enox-PS did not significantly change. The anticoagulative properties of substituted heparins were significantly attenuated compared to non-substituted compounds. The interaction of UFH-PS with HSA, lysozyme, and protamine was studied with ITC. Under serum-free conditions, UFH-PS- trans with a high DS stimulated proliferation of murine fibroblasts, while UFH-PS- cis decreased the viability of these cells. Under serum conditions, both UFH-PS- cis and UFH-PS- trans decreased cell viability, the reduction for UFH-PS- cis being higher than that for UFH-PS- trans . Neither Enox-PS- trans nor Enox-PS- cis influenced the viability at concentrations prolonging aPTT, while at higher concentrations their cytotoxicity did not differ.